1. Field of the Invention
The present invention relates to a process for isolating and purifying amino acids.
2. Description of the Related Art
Amino acids are usually produced by fermentation processes using, for example, glucose as a main starting material. The fermentation liquor obtained by such method contains, as impurities, several kinds of by-product amino acids, as well as sulfate ions, chloride ions, and pigments. This type of fermentation liquor is a typical amino acid solution which may be used according to the process of the present invention. In addition, aqueous amino acid solutions obtained by other methods may also be treated by the process of this invention.
Various processes for isolating and purifying amino acids from their fermentation liquors are known. Examples of these processes involving various amino acids will now be discussed.
Histidine may be isolated and purified from its fermentation liquor by repeated crystallization; adsorption of histidine on a strongly acidic cation-exchange resin to remove the impurities followed by elution of adsorbed histidine with a suitable eluant such as ammonia; and addition of an inorganic acid to increase adsorption [Japanese Patent Kokai No. 148094 (1976)].
Valine may be isolated and purified from a valine fermentation liquor by repeated crystallization; a specific fractional crystallization process for solutions of valine containing leucine and isoleucine which are similar in structure to valine [Japanese Patent Kokai No. 16450 (1981)]; and adsorption of valine on a strongly acidic cation-exchange resin to remove the impurities involved, followed by elution of adsorbed valine.
Processes for purifying threonine from its fermentation liquor include repeated crystallization; and adsorption of threonine on a strongly acidic cation-exchange resin to remove the impurities involved, followed by elution of adsorbed threonine with a suitable eluant such as ammonia [Japanese Patent Kokai Nos. 77090 (1973), 32693 (1979)].
Methods for isolating and purifying isoleucine from isoleucine fermentation liquors include repeated crystallization [Process for Purifying Hydrochlorides, Japanese Patent Kokai No. 62554 (1984)]; a specific fractional crystallization process for solutions of isoleucine containing leucine and valine which are similar in structure to isoleucine [Japanese Patent Kokai Nos. 16450 (1981), 123622 (1975)]; and adsorption of isoleucine on a strongly acidic cation-exchange resin to remove the impurities involved, followed by elution of adsorbed isoleucine [Japanese Patent Kokai Nos. 126878 (1975), 131550 (1981)].
A method has been proposed for isolating and purifying arginine from an arginine fermentation liquor [Japanese Patent Kokai No. 6778 (1975)], in which said fermentation liquor is brought into contact with a strongly acidic cation-exchange resin to adsorb arginine, followed by elution of adsorbed arginine with an aqueous solution of ammonia and ammonium chloride. In this case, microbial cells and a portion of the pigments are removed during the adsorption process.
The processes which have been proposed for isolating and purifying glutamine from glutamine fermentation liquors include (1) use of an OH-type anion-exchange resin to fix the impurities involved at the isoelectric point of glutamine, thereby recovering a solution of pure glutamine as effluent; or converting glutamine into a cation at a low pH, allowing the cationic glutamine thus formed to be adsorbed on a strongly acidic cation-exchange resin, then washing off unadsorbed impurities and finally eluting the adsorbed glutamine (in these processes, microbial cells and pigments are removed before or after the chromatographic opera ion) [Japanese Patent Kokai Nos. 81587 (1974), 89590 (1975), 3040 (1981)]; and (2) repeated crystallization [Japanese Patent Kokai No. 95481 (1975)].
Generally speaking, the above-mentioned crystallization processes have the disadvantage of low product yields because of the repetition of the crystallization steps. The methods involving adsorption of an amino acid on a strongly acidic cation-exchange resin to remove the impurities followed by elution of adsorbed amino acid have a problem in that such methods involve fluctuations in the pH of the system which tend to cause the amino acid to pass unadsorbed through the resin, thus resulting in low product yield.
In the case of glutamine, the ion exchange processes have the disadvantages that during the fluctuations in pH, glutamine undergoes ion exchange with the resin or passes through the resin unadsorbed, thus leading to a loss in product yield. Another disadvantage is that glutamine tends to be decomposed into glutamic acid and PCA ["Chemistry of the Amino Acids", page 1933 (1961), John Wiley and Sons, Inc.].
The processes involving the use of cation-exchange resins are further disadvantageous in that they also call for the use of acids and alkalis to reactivate the resin, and complex operation. Moreover, in the case of, for example, arginine, pure arginine cannot be isolated because by-product amino acids such as lysine, ornithine, citrulline and histidine, behave similarly to arginine under these conditions.
In spite of the above-described known methods, there is a continuing need for new and improved methods for purifying amino acids from solutions thereof.